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‘APPENDIX 1.
United States Patent p]
[II]
Fw%
[as]
Inventrx:
Sen-Maw Fang, North Salt Lake, Utah
[73] Assignee: $M$’ Labs, Ine, North Salt Lake City,
[U]
Appl. No.: 09/036,854
[22] Filed:
Mar. 9,199s
[51] Int. Cl.6 .... ..... ..... ........ .. ..-.v....................
CO% 229126
[SZ]
.
U.S. Cl . . . . .. ....‘
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.. ... ... _......." . ...." S62/560; SW567
[SS] PIeId of Search ...Al._l_.l..._._.l....,...562/560,567;
514/554,556
References
Cited
WI
5,994,581
Nov. 30,1999
T Ka&kaws et al., “EZec!s of L-Camitine on Exercise
Tolerant in Patientswith StableAngina Pectmis,”Japu-
[S4] CARNlTINE CRE4TINATE
[75]
Patent Number:
Date of Patent:
U.S. PATENTDOCUMENTS
5,030,657 7/1991 Burtle et&.
OTHEik PUBLJC/‘JlONS
DatabaseCAPLUS on STN, Act. No. 1970:404187.Nordmann et al, ‘Antiiatigue phosphocrcatiw salts. GB
1185882 (abstract),1970.
P R Bomm, “Camitine,”Ana R& Nun. 3:233-259.1983.
G Brevctti,et al. %oreasesin WaIkingDistancein Patients
with PeripheralVascularDiseaseTreatedwith L.-Camitine:
A Double-Blind, Cros.QJver Shaiy,” Circulation, 77(4):
nese HearrJoumd,
25: 587~597,1984.
S &&in, A Seven, M Mert, F Akalp, F YurdaIwl, and G
Ckdan, “Gould L-Carnitine be an Acute EnergyInduar in
Calabdic ChxIitions?“, Dev Mcd Ckifd New02 39(3):
174-177, 1997.
K Lint, S Cboi, Y S Cha, and D S Sachan,“Caruitine and
Ca&ine&mi&tration IncreasesFat Oxidationand EndurancePerfo&ancein Athletes: FASEBJ, ll(3): 2174,1997.
CM&i, K Iriyama,B K GUIISOII,
H Suzuki andP MoMaster,
“PlasmaCam&c Kinetics during Ortbotqpic Liver Traasplantation;’&and 3 GaslmMterol, 3x4): 357-362.1997.
U Rebouciie,DJ Paulson,“Camitioe Metabolismand Function in Humans,”AmRey Ntm 6:41-66,198G.
A A-Shukaji et al., “On the- Interrelationship between
Hepatic Qrnitiue, Fatty Acid Oxidation, rind TrigIycctide
Biosynthesjs$ Nephcosis:’Lip&, 32(8) 847-852‘1997.
L Vecchiel‘etaI., ‘Influence of L-CamItine Administration
on Maximal Physical Exercise,”Eur J&pi Physio7,61:
486-494%990~
Sigma-Taq PbarmacenticaIs,Inc., “Camitor,” Pkysicians
Desk Reference,pp. 2623-2625,1997.
Primary E+r-Gary
G&l
Assistant Exuminer-Brian J. Davis
76%773,1988.
Attoq,
H P Broquist, “Camitint: A %entieth Century Study,”
FMEB .7ou,t, ll(3): 2088,1997.
P Cerrcteltiand C Marconi,“L-Camitine S~@mentatian
in Humans.The Effects on PhysicalPerformance:’Iti. 3.
Sponr Med. 11: l-4, 1990.
R N Cortrigbt, D M Muoio, and G L Dohm, “Skeletal
MuscleLipid Metabolism:A Frontierfor New Insights into
Fuel Homeostasis,”
NucritionrtlBiochemistry,8: 228-245,
1997.
I R Dipalma, ‘Lcamitioe: Its Therapeutic Potential,’
AmericanFamiiy Physician,34(9:17.7~l30, 1986.
1 R Dipalma, “Camitiue Deficiency,”American Family
ABSTRACT
kv
The present invention relates to the formation of a Sal!
betweencar&w and creatincwhich has unique and us&l
attributesaver creatine mowbydratc or carritine base.An
acid-baseran&ionbetweencam&e and neatiac causesthe
formation of the salt composition.Further, the inventioo
provides a%aIt form of camitioe which is very stable and
non-hygrovopic, The camitine cnatioate product of the
presentinvention is representedby the following:
Physkkm,38(1):243-251,
*en& or Firm-Thorpe North & Western,LLP
1988.
R Fenari, F Cwchini and 0 Visioli, “The Metabolical
EffccC of L-camitine in Angina Pcctozis?I&Z J of Cardi&gy,5:
2s2X,1984.
J D Felts,AL Shug,J R K&e, N Bittar, “Ptotecfion of the
Is&&c Dog Myocardiumwith Camitine,”AmaricunJ. of
CQdfOfO~,
443120%i214,1978.
E M Gorostiaga,C A Mawr, J P Eclacha,“Decreasein
Respiratory Quotient @ring Exercise FoIIowing L-Carnitinc SuppIementaticm,”
Int. J. Sporrs&fed, 10: 169-174,
1989.
S Hirose, et al., “Car&&e DepletionduringTotal ParenteraI
Ac
Nukition DcspitcOral L-Camitiae SupplementaIion,”
PQedia~~~aJa~~ca,3~1~2~,~9~.
wherein X is an integer behveenabout 0 and 5.
6 Claims, No Drawings
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by the anaerobic degradationof phosphocreatic (PCR) and
glycngen(&ltman E. et aL;Energymer*rbolirmandfatigue.
BRIEF DESCRlPTlON OF THE INVENTION
In: Taylor A, Gollnick P, GreenH, et al., eds.Biocb~m~*~
This invention relatesto the formation of a salt between of.&&& VII. Champaign,III: Human Kinetic Publishers,
camitincand creatinewhich hasuniqueand useful attributes 5 1990: vol. 21, 73-92). Greenhaffet al. proposedthat the
observeddeclinein force production during intensecontracover creatioe monohydrate or carnitine base. More
specifically,tb6 invention relatesto a carnitinc creatinate tion may be relatedto the availability of musclePCR stores
(Grcahaff P. C., CaseyA., ShortA H., Harris R., Soderhmd
salt that provides a significantly improved taste over carnitine salts,such as tartrateand citrate,heretoforeavailable. K., Hnlimab E.; i@uence of oral creatine supprementaiion
volunAdditionally, it provides a salt form of camitine which is IO of mu& mque during repented bouts of m&l
very stableand non-hygroscopic.The combinedcompound my exercisrin man; Clinical Science(1993) 84,565-571).
The deplet@nof these PCR storeslimits the rephosphoryis an excellent choice in diet formulations because it
lation of ADP, therebylimiting the ATP availablefor energy
improvesmetabolicfat burning andprovidesan extraenergy
production. Greenhaff et al. further proposed that any
boost.
IS mechahismcapable of increasing the intramusculartotal
BACKGROUND OF THE INVENTION
creatine store ,might arrest PCR depletion during intense
muscularcontractionand offset or even prevent the decline
Creatine, also known as N-(Aminoiminomelhyl)-Nmethylglycine, methylglycoamine or N-methyl-guanido in the rate of ADP rephosphorylation during exercise.
Grcenhaff
et al. did not document means whereby the
amtic acid is listed in the MERCK INDlX, an accepted
chemical encyclopediaand may be representedby the 20 effectiveiount of creatincwitbin the musclecellscould be
increased.indeed, Grcenhaffei al. relied upon work previfollowing depiction:
ously publishedby Harris et al. where it was demonstrated
that the creatine content of skeletal muscles may be
increased,howeverby only 2@-$046,through standardoral
z pathways.,ImportanUy,in order to achieve this mediocre
increasein the.creatinecontentof musclecells the subjects
of the study were required to ingest 20 grams of creatinc
monohydrate,much of which was washed out through the
urine inste+dof being assimilatedand metabolized(Harris
(The Merck Index Tenth Edition, No. 2551). Perhaps, 30 RC, Soderhmd K, Hultman E.; Elevation of crealine in
becauseof thepositioningof the-NH, group gamma to the
resting and exercised muscle ofnormal subjects by creative
carboxylic acid, creatine is labile to acid hydrolysis.
supplemen&tion.,Clin. Sci., 1992; 83: 367-74).
Regardless,however,of any purportedrational, creatineis
Creatine’
can be found biologically in many forms and in
susceptibleto cyclization under acid conditions to form
diverseportionsof the body. Walkerreportscreatineto exist
crealinincwhich may be representedby the following depic- 35 mainly in the nerves and muscle (Walker J.B.; Crea~ine:
Biosynthesis.rcgulurion,andfuncfionAdr! Enzymologyand
tion:
RelaredA&as of Moiecular Biology (1979) 50: 177442).
Creatinehasa normal turnoverrateof about2 gramsper day.
The biochemicalprocesswhich uses creatinefor the regenF
NH
4c eration of +TP fFomADP irreversibly transformscreatineto
creatinine which is eliminated through the urine. Because
Ycreatinei&irreversibly used, the body must either produce
creatinebiochemicallyor securean adequateoutsidesource.
I0
“\E
Biochczncally creatineis synthesizedin the human liver
4s and pancreaswhereascreatineis synthesizedexclusivelyin
In acidicaqueoussolutionsthe formationof creatininefrom
the,liver by membersof the poultry family. The humanliver
creatine is nearly quantitative and irreversible (Cannan, and pancreasuse the amino acids glycine, serine,arginina
and methjonine to synthesizecreatine. However, where
Shore,Biochem. J. 22,92& 1928).Creatinineis, aswell, one
sufficient creatine is made bioavailable through ingestion
by-productof normalmetabolic useof crearineandhasbeen
used as a diagnostic marker of such use. Moreover the 50 such biosynthesiswould seemunnecessary.Although aniexposureof creatine to the acidic environmentof the gut
ma1 musqlc contains approximately 0.5% creatine by
weight, m&t of this is degradedby cooking thereby prewould be expectedto causethe irreversible formation of
creatinine precluding further biological use of ingested eluding cqoked meat from the potential list of external
creatine. Furthermore,the ingestion of crealine has been sourcesOCingestile bioavailablecreatine.Moreover,neiassociatedwith markedstomachand gastricupset.Althotigh 5s ther plant nor vegetablematterprovidesa sourceof creatioe.
the ingestionof creatincand gastic upset are perhapsonly
Creatina has been a componentin several recent U.S.
linked by empiricalobservation,the acid stability of crealine
patents.US. Pat. No. 5397,786 entitled REHYDRATION
and subsequentformation of creatinineprovide potentia1 DRINK dbclnscs and claims a rehydration drink for the
treatment$nd preventionof the lossof essentialelectrolytes
IWEOIlS.
Muscle contractionand relaxationare fueled by the free 60 becauseof Buid loss. This patent teachesthat creatine,B
energy liberated by the dcphosphorylationof adenosine vitamihs,pantothenicacid andcholineareenergyenhancers.
Additionally, tbii invention suggeststhe addition of numertriphosphate(ATP). ‘Ihe AI’P stored within ceI1.sis rapidly
depleted during even normal activity. For normal tissue
ous salts such as MgC4, CaCO, and magnesiumaspartate
function to continue, Xl? must be rapidly resynthesized assupplementswhich containessentialnutrientsfor healthy
from its breakdown products, one of which is adenosine6s metabolism.However,the useof ionic&s such as MgCO,
is less effective than desiredbecausemost of the ingested
diphosphate(ADP). During maximal exercise of a short
durationthis resynthesisis accomplishedalmostexctusively element is lost in the acidic environmentof the gut.
CARNITINE CREATINATE
‘-‘----‘,
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$994,581
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U.S. Pat. No. 5,576,316entitled METHOD FORINHIBITING TUMOR GROWTH RATE USING CREXI’INE OR
CREATINEANALOGS issuedNo?. 19, 1996. This patent
teachestbe use of creatine and creaiine analogs for the
treatmentof tumors.Specificallythis invention.teacbesthat 5
the administrationof creatinein the form of a saIt can reduce
a tumor’s growth rate. Importantly, this pat&t also teaches
that significant portions of orally administeredcreatine are
lost through the urine without having been used by the host
Although the potential causesfor this observanceare not
stated,one reasoncould be the low solubility of creatinein IO
water to account for the observed preclusion of ingested
creatinefrom biological use.
Carnitine
(3.Carboxy-Z-bydroxypropyl)
trimathylammnoniumhydroxide inner salt (CAR) may be
represented graphically according to the depiction of 15
GraphicI.
LCamitine may improve exercise tolerancein patients
with effori angha (Efffecisof L-Cartiine on Exercise Tolerance in @i&t.s with Slable At&a Pecloris. Japanese
Heart Journal 25: 587, Karikawa T. et al., 1984).
L-Carnit@+converted lactate production to extraction and
increasedthe percentageof free fatty acid extraction,suggating a qse to improvethe metabolismof coronaryartery
disease patients (The Mefabolical Ej$ects of L-Cardtim in
Angina P&%ori.s.Ferrari R., Cuccbini F., Visloli O., laternarional Journal of Cardiology 5(1984): 213-216).
L-Car&m has also improved the walking capacity of
patientswith intermittentclaudication (mCreu.se~
in WaIking
Distance &I Patients with Peripheral Vascular Dtiease
Treated v$th L-Camitine. A Double-Blind,
Cross-Over
S&y. Breyetti G., Jancelli V. G., et al. Circulation Vol. 77,
No. 4,76%-7X$ April 1988). L-Camitine may benefit the
ischemicmyocardinmby maintaining tissue levels of free
cardine
Ompbic
I
20
(Protection of the Ischetic
Dog Myocardium wilh
Camitine..Folts J. D., Shug A. L., Koke 3. R., Bittar N.,
American Journal of Cardiology 41: 1209, 1978).
Pat&& wifh type II or type IV hy+ipoprotcinemia,
when treatedwith 3 grams of oral camitine per day, had a
marked reduction in serumcholesterol and serumtriglyceridc (Car&&e. Bornm, P. R. Ann Rev Nutr 1983. 3:
233-259).
Carnit$e may be an essentialnutrient for the newborn
(Car@inqc Bmum, P. R. Ann Rev Nun 1983. 3: 233-259).
L-Camitine has promisein reducing the fat accumulationin
certain types of fatty Iivers (L-Car&tie: its Therapeutic
PotentiaL Dipalma J. R. Amer Fan Phys 34(6): 127-l30,
1986). The use of L-Car&& in dialysis patients may be
important’iu individual cases L-Camnitine: Its Therapedc
Poren~ial. ,Dipalma J.R. Amer Fam Phys 34(6): 12%l30,
There are two chemical forms of CAR, L-CAR and
D-CAR, OCwhich LCAR is biologically active and is 25
pharmaceutically available for medicinal indications.
Biologically, a portion of CAR binds fatty acids forming
acyl (A) CAR while the restexistsas free (F) CAR. The sum
of thesetwo fractions &referred to as total (T) CAR Some
of its physiological roles in fatty acid oxidation and in the 30
excretionof organic acids have been well investigated.
LCamitine functions as a carrier moleculein the transport of long chain fatty acidsacrossthe inner mitocbondrial
membrane.It delivers substratefor oxidation and subse- 1986).
quent energyproduction.
Meat and dairy productsarethe major sourcesof carnitioe
Camitine’s essentialrole is to transport fatty acids of 35
in the United States.Cereal,fruits, and vegetablescontain
12-18 carbonsacrossthe outer and inner membranesof tbe
little or no carnitine (Carniiine. Borum, I? R. Ann Rev Nutr
mitocboodria.Camitine palmitoyltransferasecatalyzestbe
1983. 3: 233-259).
transfer of the fatty acid or acyl group to camitine at the
Individuals on enteral nutrition for long
of time
outer surfaceof the mitochondrialmembrane.The acylcar, periods
mxare,
caseIn,
or egg
nitine then goes acrossthe outer membraneof the inner 40 WhOSo pIOteln SOuTCe 1s sOy pmeln
white
protein
get
low
amounts
of
carnitine
(4
nmoliml
surfaceof the mitocboodrialmembrane.Here the acyl group
camitioe
br
Iess)
(Carni~ine.
Bornm,
P.
R.
Ann
Rev
Nurr
is transferredback to coenzymeA under the inlinen- 01
cam&e paimitoyltransferase II (Carnirinu Deficiency
1983. 3: p3-2.59).
DipalmaJ. R.,AmericanFamifyPhysician,
38(I): 243-251,
There is evidence of increasedVO, max with carnitine
1988).
45 suppleme@ation.
This is probably through the removal of
L-Carnitioe is used in the treatmentof primary systemic part of the short-chain acyl-CoA by L-Camnitine in the
carnitioedeficiency.CIinicaI presentationcan include recurmuscles heavily involved in exercise with a concnrreot
rent epis&es of Reye-like encepbalopathy,bypoketotic
releaseof free CoA. This would stimulate pyruvate debyhypoglycemia, and/or cardiomyopathy.Other associated drogenasqand enhanceflux in the Krebs Cycle(L-Carnitine
symptomsincludedhypotonia,muscleweakness, andfailure SO Supplemwtafion in Humans. The Effects on Physical Perto thrive (Physicians Desk Rq%wnce, 1997, p. 2624).
formance, Cerretelli P., Marconi C., Int J. Sports Med 11
L-Carnitine may also alIeviate the metabolic abnormali- (1990) 1114).
ties of patientswith Inborn errors of metabolismthat result
L-&&tine
could be advantageous to exercising
in the accumulationof toxic organic acids(Physicians Desk
individuais, as prolonged exercise increasesthe urinary
55 excretion, of camitioe (L-Carnifine Supplementasion in
Reference, 1997, ~2623).
Camitine’simportancein cardiac metabolismand funcHumans.!t?zEffects on PhysicalPerformance. Cerretelll P.,
tion hasbeenemphasizedby a numberof studiesshowing a
Marconi C., Int J. Sporfs Med ll(1 990) l-14).
close associationbetweensystemicand myopathiccamitine
A positive effect of L-Camitine is au increaseof muscles’
deficiencyand both bypertropbicand congestivecardiomyo- anaerobiccapacity. Carnitine, by fnoctiomug as an acetyl
patbies (Cam&e Metabolism and Fun&n in Humans. 60 group buffer, 1) Maintsios a viable pool of CoA even when
ReboucheC. I., PaulsonD. J., Ann Rev 1986. 6: 41-66).
the rate cif acetyl-CoAformation exceedsthat of condensaReportsindicate L-Camitine therapy converts abnormal tion of the above metabolitewith oxaloacetate,2) Prevent
fatty acid metabolismto normal, increasesthe concentration ‘%oodin$’oftbe mitochondrialmatrix by acetyl-CoAesters,
of LCamifine in cardiacmuscleaod in blood, and improves 3) Act as an additionalsink for pyruvare,and 4) Improve the
cardiacoutput and blood pressure(L-Cam&e: Its Thera- 65 transport pf adeoiaermcleotides(L-Carnitiw Supplementapeuric Potential. Dipalma J. R. Amer Pam Phys 34(6):
tion in Humans. The Effects on Physicul Pe$ormance.
127-130,1986).
Cenetelli P., Marconi C., InlJ. SpowMed 11 (1990) l-14).
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L-Camitine may increaselipid utilization by muscleduring exe&e. (Decrease in Respiratory Quotient During
Exercise Following L-Camitine Supplementation. GorostkagaE. M., Maurer C. A., E&&e J. P.,Inr J. Sporrs Med.
6
properties of the salt comprising creatine and car&me,
namelycacnitinecreatinate,areunexpectedin that the salt is
more stab)r:than the two organic moieties of which it is
made and has a distinct yet pleasant taste.
5
Furthermore,carnitinecreatinate salt of the presentinvention is a u&me chemicalcomposition as evidencedby the
designationof a ChemicalAbstracts Serviceunique identifer. This unique identifer is given to new chemicalcompositions by the Chemical Abstracts Service (CAS). The
10 uniqueCAS numberassignedthe unique camitinecreatmate
chemical compositionof the present invention is 20179031-O.
10 (1989) 169-174.
LCarnicine has been showy to increaseboth maximal
oxygen uptake and power output (InjJnenceof E-Carnirine
Adminisrrationon Maximal PhysicalExerc&e.VecchietL.,
et al. European Jounuzl @Applied Physiology (1990) 61:
486-490).
In the supplementationof L-CAR for patients on longterm total parenteralnutrition, especiallyfor patients with
shortbowel syndrome,a morepracticalproblemarises.Oral
supplementationof L-CAR of the type known cannot propREFERREDEMBODIMENT AND EXAMPLES
vide a sufficientamountof CAR when patientshave severe 15
A
preferredembodimentof lhe present invention would
malabsorption, because it is not easily absorbed.For this
population, intravenous supplementationis considered. be preparedaccordingto the following:
However,the availability of L-CAR 601ihtravenousadminEXAMPLE 1
i&ration is limited becauseof a lack of metabolicallyacceptable salts of car&me.
One mole of camiline (161.20 grams) is mixed with one
20
Camitine possessesan unpleasantsmell and is hygromole of cmatinemonohydrate(149.15 grams)in a 4:l w:w
scopicas a solid. The hygroscopicitymakesit very difficult
mixture of isopropanol(40 g):water (10 g). The mixture is
lo store camitine,especiallyas a solid. Tbe creaturesalt of
heatedIO 70-72 C. until the mixture becomesa soft mass.
carnitineof the presentinventionovercomestheseproblems Continued,mixing for an additional 5 minuteswith subseand possessesa distinct yet pleasanttasteand is not hygro- 2s quent coolingto 15-20’ C. resultsin a solid material.The
solid ia further dried at reducedpressure(400-500 mm Hg)
scopic.
at no higher than 45” C. The resultant &n&e creatinale
OBJECTSCtFTHE INVENTION
monohydr&esalt has a molecularweight of 310.35 with a
decompositionmelting point of 184-188’ C. and is a nonIt is thereforean object of the presentinventionto provide
30 hygrosco$c solid with a distinct yet agreeabletaste.
a salt of carnitine with crealine.
The salt synthesizedaccording to this example can be
It is ao additional object of the invention to provide a
caraitine salt having improved palatability and decreased administeredin daily dosagesofbehveen about50 and2,000
mg/day.Such dosagescan be in a single doseor m divided,
hygroscopicity.
It is still another object of tbe invention to provide a 35 multiple doses.The salt can be pressedinto tablets,placed
in
capsules,formulated as a syrup or elixir, or preparedby
creatinesalt of camitinewhich hasimprovedpalatabilityand
anv other conventional mechanism for oral dosane.
metabolicavailability.
Preferably,becauseof its improved palatability, the salcm
Theseand other objects may be accomplishedby means oowder form can be administeredbv disnersineor dissolvof an organicsalt formed of crcatineand camitine and their
&g it in a drink such as fruit juice. 1; ma; alsogc combined
attendant salts and ananalogue.As used herein&e term 40 with protein powders or other food sourcesdesignedto
“camitine analogue”will connote a salt or derivative of
improve metabolicperformance.
carnitine such as a memberselectedfrom tie group consistingof carnitinehydrochloride,carnitineesters,camitine
EXAMPLE 2
amides,camitineimides and mixmresthereof.Similarly,the
Apanelspf
ten
people
were given samplesof a mixture of
term “creatine analogne”will connotea substancewhich is 4s
100 mg of creatinemonohydrateand 100 mg of carnitinein
made from chemicalmanipulationof creatine.
250 ml of applejuice. The samepanel was given 200 mg
carnitinecreatinateformed in Example 1 in 250 ml of apple
DETAILED DESCRIPTIONOF THE
juice. The sampleswere merely labeled A and B and each
INVEN’IlON
Both creatineand camitine are bimorphic,each contain- 50 memberof the panel was free to elect which sampleto taste
first. In ail instancesthe sample containing the carnitine
ing an acidicand a basicmoiety.This somewhatunique dual
oreatinatesaltwas judged to have the better taste.
charactercreatesa natural analogy between creatine and
carnitine,the correspondingsalt formed,and analogoussalts
EXAMPLE 3
of ammo acids.Amino acids also possessboth acidic and
basic moietieswithin one molecularstructure.Becauseof 55 The resultantcarnitine creatinatesalt, in solid form from
Example 1, in dosagesof from about 50 to 2000 mg, can be
this dual nature,aminoacids,creatine,and carnitincmay be
mixed with 8 oz. water or juice and taken as an exercise
either the anionic or the cationic portion of a salt which
supplement This supplement can be taken in single or
includes them. Specifically these dual functionality comdivided dosessuch that
pounds
can-be used
as either the. . acid or the
base
in the
. between50
. mg. to
_ 2000 mg of the
^
.
.
.
.
tormabonat a salt throughan acid-Lme reaCtlOd. MOreOVer, 60 camitine creatinatesail 1smgestedeach 24 hour period.
these dual functionality organic compounds often form
While me above example shows a 1:l molar ratio of
interior, intramolecularsalts, e.g. a.salt formed of its own
creatineto camitine to form a salt, the molar ratio may vary
from bet&en aboutO.l:l to 1:O.l creatureto camitine. This
acidic and basic portions. Carnitine is an a-hydroxy carboxylic acid and creatine is an a-N(aminoiminomethy1) may be accomplishedbecausecreatine and camitine form
carboxylic acid and the acid-basereaction between these 6s stable salts internaIly. Indeed,one of skill in the art would
utxbrsttm@the various ratios and mannersin which these
two causesthe formation of the salt compositionwhich is
one embodimentof the presentinvention. Importantly the
two organic compoundsmay be advantageouslycombined.
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What js‘clsimed is:
In summary,it ia to be noted that creatineis an important
1. A salt of a creatine member and a camitine member
factor in the regenerationof ATE Camitine is an essential
wherein the molar ratio between the creatine memberand
cofactor far many metabolic interactionsin the body parthe carnitine memberis between about 0.13. to 1:O.l.
titularly in the role of fatty acid oxidatron and in the
2. The salt according to claim 1 wherein the creatine
excretionof organic acids.Both creatineand camitine have s member
i$ selectedfrom the group consisting of creatine,
a characteristicunpleasanttastewhen administeredorally.
cmatine esters,cnatine amides,creatine imides, and mmMoreover, creatine monohydrate is only slightly water
tures thereof.
soluble.Additionally inorganicand internal saltsof cam&e
3. The salt according to claim 2 wherein the carnitine
areunstableandhygroscopic.The camitinecreatinatesalt of 1n member is’selectedfrom the group consisting of camitine,
carnitine esters,camitine amides,camitine itnides,camitine
the presentinventiongreatly nnprovespalatability andoveranmoniq s&s, and mixtures thereof.
all stability and enabiesthe optimal biofnnctionality of both
4. The salt according to claim 2 wherein the creatine
creatine and camitine in enhancingenergy and metabolic
member is creatine.
rates.
5. The salt according to claim 4 wherein the carnitine
Furthermore,significant publications and researchhave 15 member is camitine.
&The salt accordingto claim 5 being representedby the
concluded that nitrogen metabolismand growth are proformula:
mated by CAR ingestion,with somestudiesconcluding that
CAR injection should be a part of normal TPN, especially
for pediatric patients. However, the instability and marked
bygroscopicityof camitine hasmadesuch use digicult The 20
present invention amelioratesthis and other concernsby
providing a camitine salt which is stable and non hygroscopic. Moreoverthe salt of the present invention accom+X Hz0
plishesthis benefitwhile providing the unexpectedadditive
25
advantageof assistingin muscleenergy stores.
Therefore, the salt of the present invention is more
beneficial than a simple mixture of inorganic salts of carnitine and creatinebecausethe camitinecreatinatesaltof the
present invention is nonhygroscopic. Furthermore, the
present invention provides for improved palatability and 3o wherein X is an integer between about 0 and 5.
I * * * *
would be better acceptid by the user.
http://patimg2.uspto.gov/.piw?docid=USOO59945Sl&PageNum=5&IDKey=FFl4EBEBB...
12/2/2003